Intestinal lactase deficiency in an apparently normal Peruvian population

The prevalence of milk and lactose intolerance and intestinal lactase deficiency was studied in 30 apparently healthy Peruvian individuals. At the same time, 20 milk-intolerant persons were included in the study. According to the results of lactose-tolerance tests and intestinal lactase assays, one-third of the 30 were considered normal and were used as controls. The other two-thirds were found to be abnormal and were referred to asasymptomatics; they tolerated well small amounts of milk consumed daily. Upon lactose load, they developed gastro-intestinal symptoms, and maximal rise of blood glucose was below normal limits. Enzymatic assay indicated that they were deficient in intestinal lactase. The remaining 20 were intolerant to milk and the results of their tests were abnormal. Sucrase activity was similar in the 3 groups. This high incidence of lactase deficiency in apparently normal individuals seems to be acquired.     

乳糖酶缺乏与乳糖不耐受症状的临床特点分析

目的 探讨乳糖酶缺乏及乳糖不耐受症状的临床特点.方法 回顾性分析了84例于广东省人民医院门诊就诊的以腹痛、腹泻、腹胀、肠鸣为主要症状的患者,并接受胃肠镜、腹部CT、抽血及氢呼气试验等检查评估,根据患者的主要诊断,氢呼气试验结果及乳糖不耐受症状进行分组,比较各组的临床指标,包括年龄、性别、体质量指数、血常规、过敏原检测、...     

Lactose malabsorption, irritable bowel syndrome and self-reported milk intolerance

BACKGROUND: The relationship between lactose malabsorption, irritable bowel syndrome and development of intestinal symptoms is unclear, especially when the ingested dose of milk is small. Thus, the role of hydrogen breath testing in the diagnostic work-up of patients with nonspecific intestinal symptoms is still debated. AIMS: To establish the relationship between lactose malabsorption, severe self-reported milk intolerance, irritable bowel syndrome and related symptoms. METHODS: The prevalence of lactose malabsorption was prospectively assessed by means of a hydrogen breath test in 839 patients (503 with irritable bowel syndrome, based on the Rome criteria, regularly consuming milk, and 336 subjects who identified themself as milk intolerant, after an oral load of 25 g lactose). The test was considered "positive" when a hydrogen peak exceeding 20 ppm over baseline values was observed in two or more samples. Attempts were also made to establish whether the predominant presenting symptom (diarrhoea, constipation, alternating diarrhoea and constipation, pain and gaseousness) might be helpful in predicting the outcome of the breath test. RESULTS: The prevalence of a positive breath test was comparable in the two groups (337 patients with irritable bowel syndrome (66.9%) vs 240 patients with milk intolerance (71.4%)). The same holds true for the first peak of hydrogen excretion, total hydrogen output and prevalence of symptoms during, and in the four hours after, the test. The predominant presenting symptom was not useful for predicting outcome of the test either in regular milk users or in milk intolerant subjects. CONCLUSIONS: The almost identical results of the lactose breath test of patients with irritable bowel syndrome and subjects with self-reported milk intolerance suggests that the two conditions overlap to such an extent that the clinical approach should be the same. A lactose breath test should always be included in the diagnostic work-up for irritable bowel syndrome, as fermentation of malabsorbed lactose is likely responsible for triggering symptoms. Conversely, lactase deficiency is probably irrelevant in most subjects not affected by irritable bowel syndrome, within a moderate milk consumption.     

The Importance of Milk Intolerance in Patients Presenting with Chronic (Nervous) Diarrhoea

Summary: Lactose barium study and/ or lactose tolerance test were used to screen for milk intolerance in cases presenting with chronic (nervous) diarrhoea. Of 19 cases, 18 were found to be intolerant to milk, showing that lactase deficiency is a very important aetio-logical factor in chronic (nervous) diarrhoea in Singapore. Withdrawal of milk was followed by rapid improvement in all the affected cases.     

Lactose malabsorption and intolerance: What should be the best clinical management?

Lactose malabsorption (LM) is the incomplete hydrolysis of lactose due to lactase deficiency, which may occur as a primary disorder or secondary to other intestinal diseases. Primary adult-type hypolactasia is an autosomal recessive condition resulting from the physiological decline of lactase activity. Different methods have been used to diagnose LM. Lactose breath test represents the most reliable technique. A recent consensus conference has proposed the more physiological dosage of 25 g of lactose and a standardized procedure for breath testing. Recently a new genetic test, based on C/T13910 polymorphism, has been proposed for the diagnosis of adult-type hypolactasia, complementing the role of breath testing. LM represents a wellknown cause of abdominal symptoms although only some lactose malabsorbers are also intolerants. Diagnosing lactose intolerance is not straightforward. Many non-malabsorber subjects diagnose themselves as being lactose intolerant. Blind lactose challenge studies should be recommended to obtain objective results. Besides several studies indicate that subjects with lactose intolerance can ingest up to 15 g of lactose with no or minor symptoms. Therefore a therapeutic strategy consists of a lactose restricted diet avoiding the nutritional disadvantages of reduced calcium and vitamin intake. Various pharmacological options are also available. Unfortunately there is insufficient evidence that these therapies are effective. Further double-blind studies are needed to demonstrate treatment effectiveness in lactose intolerance.     

Efficacy of Addition of Exogenous Lactase to Milk in Adult Lactase Deficiency

The efficacy of lactase by Kluyveromyces lactis in hydrolyzing milk lactose and reducing milk intolerance symptoms was tested in 52 proved lactose malabsorbers. The enzyme was added to milk administered to the patients, and H2 breath excretion (as an index of carbohydrate malabsorption), was determined by gas chromatograph technique, and milk intolerance symptoms were recorded. H2 mean excretion was 78.3 +/- 5.49 ppm after administration of intact whole milk 500 ml (test A), 43.5 +/- 4.99 ppm when lactase 2000 U was added to milk 500 ml immediately before administration (test B); 36.7 +/- 5.01 ppm when milk 500 ml was incubated for 12 h with lactase 1000 U (test C), and 29.7 +/- 4.35 ppm when the incubation was prolonged for 24 h (test D). Symptoms score was: test A = 5.85 +/- 0.56, test B = 3.71 +/- 0.45, test C = 2.77 +/- 0.63, test D = 1.7 +/- 0.68. A correlation index of r = 0.44 (p less than 0.01) was obtained between reduction in H2 mean excretion and reduction in symptoms score of a single individual. The addition of this lactase to milk seems to be effective in correcting lactose malabsorption, thus representing a convenient approach in milk intolerance.     

Lactose intolerance in active Crohn's disease: clinical value of duodenal lactase analysis.

BACKGROUND: Patients with active Crohn's disease (CD) often report having abdominal symptoms after ingestion of milk products, but the pathomechanism for lactose malabsorption seems to be complex. GOALS: To investigate the prevalence of clinical milk intolerance and to objectify symptoms with hydrogen (H 2 ) breath testing, analysis of lactase protein, and enzyme activity in the duodenal mucosa in patients with CD and in healthy controls. STUDY: In 49 patients with CD and 24 controls, H 2 breath testing was performed. All individuals underwent endoscopy of the upper gastrointestinal tract, in which multiple pinch samples were taken from the distal duodenum. Lactase activity was measured using the method of Dahlquist. The lactase protein expression was analyzed by gel electrophoresis using the monoclonal antibody mlac 10 and by immunochemistry using the monoclonal antibody mlac 4. RESULTS: Prevalence of milk intolerance in healthy controls was 16.6% versus 46.9% in patients with CD, with a high frequency (83.3%) in patients with active disease (CD activity index >150). Milk intolerance was correlated to the duration of inflammatory bowel disease ( p = 0.023) but not to the location or previous bowel resection. Hydrogen breath testing had a moderate sensitivity in detecting lactose maldigestion (70.4%) and a high specificity (95.6%). Duodenal lactase levels were also correlated to disease activity, whereas correlations to clinical symptoms remained poor. Patients with milk intolerance had a significantly reduced bone density at the lumbar spine (z-score, -1.33 +/- 0.92 vs. -0.19 +/- 0.95 [mean +/- SD]; p = 0.002) CONCLUSIONS: Milk intolerance is a frequent problem in active CD, which can be objectified accurately by H 2 lactose breath testing. Decreased lactase levels in the duodenal mucosa may be found during an acute flare but are not the predominant cause of milk intolerance in CD.     

Lactase deficiency and lactose intolerance-related symptoms in adult healthy subjects from western France]

The prevalence of lactase deficiency (LD) and lactose intolerance is not well known in France. Using breath hydrogen and methane analysis after 50 g oral lactose load, we investigated the prevalences of LD, lactose intolerance, and methane producer status in 102 healthy adults born in western France, and we examined the relationships between these parameters and the daily milk consumption. In 10 subjects with LD and lactose intolerance, we studied the reproducibility of the lactose hydrogen breath test results for the diagnosis of LD and lactose intolerance and estimated the quantity of lactose malabsorbed in comparison with the lactulose hydrogen breath test. The prevalence of LD was 23.4 percent and symptoms of lactose intolerance were observed in 50 percent of the 24 subjects with LD. The daily milk consumption was not significantly different in the 24 subjects with LD and in the 78 subjects without LD (281 +/- 197 vs 303 +/- 217 ml/24 h). The prevalence of methane producer status was 42.1 percent. The symptomatic group of lactose malabsorbers (n = 12) was characterized by a shorter lactose mouth to caecum transit time (39 +/- 20 vs 88 +/- 48 min; P less than 0.05), and more marked hydrogen production (6.1 +/- 2.3 vs 3.4 +/- 2.4 10(3) ppm.min; P less than 0.04). In the 10 subjects with LD and lactose intolerance, the hydrogen breath test was reproducible for diagnosis of LD and lactose intolerance, and for hydrogen production. The quantity of lactose malabsorbed was 60 percent. In France, symptoms of lactose intolerance are not severe and do not affect the daily consumption of milk and dairy products.     

Double blind study of milk lactose intolerance.

One hundred and fifty subjects were studied in a double blind fashion to determine the relationship between lactose malabsorption and milk lactose intolerance. Each participant received 250 ml of a different type of milk on 3 consecutive days. Milk A contained no lactose, milk B had 12.5 g, and milk C contained 37.5 g of lactose. After the experiment was completed each subject was classified with a lactose tolerance test as having "sufficient" or "insufficient" lactase activity. Milk A produced no gastrointestinal symptoms in either sufficient or in insufficient persons. Milk B produced symptoms in 3.8% of sufficient and 37.1% of insufficient individuals, and Milk C induced symptoms in 7.6% of sufficient and 83.5% of insufficient subjects. These differences are very highly significant (P less than 0.0001). It is concluded that lactose-intolerant subjects are indeed milk-intolerant and that the frequency with which symptoms occur in persons with lactose malabsorption increases in direct relation to the lactose content of the milk.     

Lactose digestion by human jejunal biopsies: the relationship between hydrolysis and absorption.

The relationship between lactose hydrolysis and absorption of released glucose was investigated by determining the kinetics of lactose digestion by jejunal biopsies incubated in vitro. Lactase activity in intact biopsies correlated with conventional assay of tissue homogenates (r = 0.85, p less than 0.001), and glucose uptake from 28 mM lactose was directly proportional to lactase activity (r = 0.95, p less than 0.001) in 21 subjects with normal lactase levels, six with hypolactasia (primary or secondary to coeliac disease) and two with lactose intolerance but normal lactase activity. Kinetic analysis at 0.56-56 mM lactose in five normal subjects showed saturable kinetics for hydrolysis (app Km = 33.9 +/- 2.2 mM; app Vmax = 26.5 +/- 1.1 nmol/min/mg dry weight) but glucose uptake could be fitted to a model either of saturable uptake (app Kt = 47.2 +/- 0.3 mM; app Jmax = 14.1 +/- 0.2 nmol/min/mg) or saturable uptake plus a linear component (app Kt = 21.3 +/- 1.15; app Jmax = 4.59 +/- 0.12; app Kd = 0.093 +/- 0.010 nmol/min/mg/mM). The proportion of glucose taken into the tissue did not significantly exceed 50% of the total released at any lactose concentration suggesting the lack of an efficient capture mechanism for the released glucose. The results suggest that lactose hydrolysis is the rate limiting step in the overall absorption of glucose from lactose in vitro, and that the relationship between hydrolysis and absorption is the same in normal subjects and in hypolactasic subjects.     

Lactose tolerance in lambs with rotavirus diarrhoea.

It has been suggested that lactose malabsorption is an important factor in producing the diarrhoea of acute rotavirus infection. Accordingly, the lactose tolerance of gnotobiotic newborn lambs, infected with lamb rotavirus, has been investigated by clinical studies and tissue enzyme assays. Although lactase activity is low in affected areas of the small intestine, rotavirus infected lambs are not lactose intolerant as assessed by the measurement of reducing substances in the faeces, or by the clinical effects and blood glucose levels after a 5.8 mmol (2 g)/kg lactose load on the second day post-infection. Lactose intolerance could be demonstrated by using extremely high (29.2 mmol (10 g)/kg) doses of lactose, three or four times the normal dietary lactose intake. These experiments suggest that lactose-containing feeds (such as maternal milk) are not necessarily contraindicated in patients or animals with rotavirus diarrhoea.     

Primary lactase deficiency in Greek adults

The incidence of lactose intolerance, studied by the lactose tolerance test (LTT), was found to be 44.7% in 600 continental Greeks, 56% in 50 Cretans, and 66% in 50 Greek Cypriots, the difference between the first group and the two other groups being statistically significant. Symptoms of intolerance during the test occurred in 44%, 56%, and 66% of the three groups respectively. Intestinal disaccharidase activity assayed in 50 subjects of the first group demonstrated lactase deficiency (lactase<2.0 units) in 21 cases (or 42%). A survey of milk-drinking habits has demonstrated that this parameter follows the pattern of lactose intolerance in the groups under consideration.     

Changes in plasma free fatty acid concentration following oral lactose tolerance tests as a test for lactose absorption in infants and children

Changes in blood glucose and plasma free fatty acid (FFA) following oral lactose tolerance tests (LTT) were measured in three groups of children. In three out of seventeen infants with secondary lactose intolerance, only a small increase (less than 25 mg/100 ml) in glucose was found, but a normal decline (more than 50% of fasting value) in FFA concentration occurred. Resumption of milk feeding proved that they were not intolerant to lactose. Six infants (37%) without lactose intolerance who were on a normal lactose-containing diet showed only small increases in glucose; five of them showed a normal decline in plasma FFA. Nine out of thirteen children with no symptoms following oral LTT failed to show an increase in blood glucose, while in only one there was a decline of less than 50% in FFA concentration. Our results suggest that measurement of plasma FFA following oral LTT may be a more reliable test for cleavage and absorption of lactose than LTT alone, but for the final evaluation of this test a study of larger groups is obviously needed.     

Lactose tolerance in a Slavic population

In order to gather data on the frequency of primary lactase deficiency in various population groups, lactose tolerance tests were performed on 38 healthy adults of Slavic origin who had recently left Eastern Europe and are presently living in Western Canada. Twenty-one of the subjects were born in Poland and 17 in Czechoslovakia. There were 16 males and 22 females, aged 17–65 years, with a mean of 29.8 years. The tests revealed that 9 (23.9%) of the 38 subjects were lactose intolerant on the basis of both criteria, showing a maximum rise in blood glucose of less than 20 mg/100 ml above the fasting blood glucose level after ingesting 50 g of lactose, and experiencing gastrointestinal symptoms during the test. The mean maximum rise in blood glucose was 39.1 mg/100 ml in the 29 lactose tolerant subjects and 7.3 mg/100 ml in the 9 lactose intolerant subjects. Gastrointestinal symptoms during the test were observed in all 9 subjects with a low rise in blood glucose, and no symptoms were produced in any of the 29 subjects with a significant rise in blood glucose (> 20 mg/100 ml). Most of the subjects consumed 1 cup of milk per day. In addition, they were irregularly consuming lactose-containing products such as ice cream, chocolate drinks, etc. The results suggest a relatively low frequency of lactose intolerance among Eastern Europeans of Slavic origin, and in this respect, they resemble Northern Europeans.Supported by grants from the National Research Council of Canada (A6249), and from the Committee on Research of The University of British Columbia (26–9682).The author wishes to thank Dr. J. A. Birkbeck for his assistance.     

Possible therapeutic use of loperamide for symptoms of lactose intolerance.

OBJECTIVES: To examine a potential practical therapeutic use of loperamide (Lo) to decrease the symptoms of lactose intolerance. SUBJECTS AND METHODS: Nineteen (eight men, 11 women) healthy lactose maldigesters (18 of 19 with symptoms) underwent a 25 g lactose challenge on five separate days. Breath hydrogen was measured, areas under the curve (AUC) were calculated for 4 h, and 4 and 12 h symptom scores were recorded. After establishing baseline measurements, test doses of 4 mg, 8 mg and 12 mg Lo were randomly administered without placebo in a double-blind manner. As well, each subject received seven lactase tablets, in a random, unblinded manner. RESULTS: The median AUC and mean oral cecal transit time followed dose response expectations; however, only lactase treatment achieved significance. Nevertheless, 8 mg Lo significantly improved symptom scores, which were statistically indistinguishable from those of lactase. Four subjects complained of delayed constipation and cramps with various doses of Lo. CONCLUSIONS: Lo monotherapy for lactose intolerance is not economical and may have some side effects. However, Lo may be studied further as an adjunctive treatment of lactose intolerance in an effort to reduce the need for complete lactose digestion. Such a manoeuvre may allow rapid colonic adaptation, which in turn may be beneficial for prophylaxis for a number of colonic diseases.     

Reinvestigation of lactose intolerant children: lack of correlation between continuing lactose intolerance and small intestinal morphology, disaccharidase activity, and lactose tolerance tests.

Thirty children on a lactose-free diet aged from 2-38 months who had previously been diagnosed as having secondary lactose intolerance were reinvestigated on 32 occasions by an oral lactose tolerance test, small intestinal biopsy, and measurement of disaccharidase activity in order to detect the presence of continuing lactose intolerance before reintroduction of milk. No correlation was found between continuing lactose intolerance, as diagnosed by the development of watery stools containing excess reducing substances after an oral load of lactose, and maximum blood glucose rise during a lactose tolerance test, lactase levels, and small intestinal morphology.     

Primary adult lactose intolerance in the Kivu Lake area: Rwanda and the bushi

In order to investigate the ethnic differences of lactose intolerance in the Bantu and Hamitic races, lactose loading tests were performed on the populations living around Kivu Lake in central Africa. In addition to the blood sugar rise the identification of the urinary sugars after the loading test was found to be a useful criterion for the diagnosis of lactose intolerance. Two out of 27 Tutsi (7.8%), 21 out of 36 Hutu (58%), 17 out of 22 Twa (77%), and 27 out of 28 Shi (96%) were lactose intolerant. These frequencies are not linked with the actual milk-drinking habits. Of 3 Twa families, 2 were mostly lactose intolerant, whereas the third was predominantly tolerant. For 11 mixed-bred Hutu-Tutsi the frequency of lactose intolerance was 55%. The results are in favor of a genetic origin of lactose intolerance.     

Effect of Ulcer Surgery on Disaccharidase Activities of the Small Bowel and on Lactose Absorption

In 14 patients with peptic ulcer, admitted to hospital for surgical treatment, the lactose tolerance test and a small-intestinal biopsy with disaccharidase (maltase, sucrase, lactase) assays were performed before and 1 month and 6 months after operation. In 10 patients without evident organic disease of the gastrointestinum, the small-intestinal biopsy with disaccharidase assays was repeated at an average interval of 1 week, and these form the control group. The mean maltase, sucrase and lactase activities in the 1 and 6-month follow-up studies were increased over the preoperative values. When the changes were compared with the alterations noted in the control group, no statistically significant difference could be noted. In 3 patients with small-intestinal lactase deficiency the symptoms following lactose tolerance test became worse in one and a history of milk intolerance appeared in one after ulcer surgery.     

Lactose intolerance in Jewish patients with ulcerative colitis

Seventy patients with ulcerative colitis had lactose tolerance tests. Of 51 non-Jewish patients, 12 (23.5%) had lactose intolerance, whereas of 19 Jewish patients, 16 (84.2%) had lactose intolerance. This difference is significant (P<0.001). The control group of 41 Jews without ulcerative colitis had a 71% incidence of lactose intolerance, whereas of 53 non-Jewish controls, only 20.7% had such intolerance. These results are also statistically valid (P<0.001). This suggested that segregation of the genes for ulcerative colitis as well as for lactase deficiency in Jews is a possible reason for the high incidence of lactase deficiency found in patients with ulcerative colitis.Supported by a grant from The Hartford Foundation.     

All Lactase Preparations Are Not the Same: Results of a Prospective, Randomized, Placebo-Controlled Trial

Objective: To compare the efficacy of three commercially available oral lactase preparations in adults with lactose intolerance. Methods: Design—Prospective, randomized, placebo-controlled trial. Setting—Outpatient study in a General Clinical Research Center. Subjects—Ten lactose-intolerant healthy volunteers were challenged with ice cream containing 18 g of lactose. Lactase or placebo was given immediately prior to challenge. Measurements—Symptoms and breath hydrogen excretion were recorded for 3 h following lactose challenge. Results: The three products differed in their abilities to influence symptoms and breath hydrogen excretion. Only Lactaid reduced the breath hydrogen excretion with lactose (mean peak, area under the curve and cumulative breath hydrogen excretion) ( P < 0.05). Lactrase and Dairy Ease influenced symptoms: Lactrase reduced pain, bloating and total symptomatic scores ( P < 0.05), whereas Dairy Ease only reduced pain ( P < 0.05). Lactaid administration did not reduce symptoms. Conclusion: In lactose-intolerant subjects, the available lactase preparations differ in their ability to improve both breath hydrogen excretion and symptoms. Lactrase may be the product of choice for achieving symptomatic improvement.